My long-term research goal is to establish how stimulation of trigeminal nerves that innervate the face and nasal passages reflexly modulate cardiorespiratory control mechanisms within the mammalian brainstem. Stimulation of the nasal passages can produce a powerful functional reorganization of the cardiorespiratory system that includes apnea, bradycardia, and a sympathetically mediated alteration of peripheral vascular tone. Although the afferent and efferent aspects of the nasopharyngeal reflex are well characterized, the brainstem circuitry that links the afferent stimuli to alteration of peripheral vascular tone is still unknown. Because sympathetic premotor neurons within the rostral ventrolateral medulla (RVLM) play a crucial role the tonic and phasic regulation of blood pressure, it is hypothesized that these neurons are important mediators of the vasoconstriction seen during the nasopharyngeal reflex. Therefore, the objective of this proposal is to investigate the relationship between initiation of the nasopharygeal reflex and activation of presympathetic neurons located in the RVLM. Specifically, does the increase in arterial blood pressure seen after nasopharyngeal stimulation occur through activation of spinally projecting C1 RVLM neurons, or spinally projecting non-C1 RVLM neurons? I propose three separate but related aims. Aim 1: Are RVLM neurons activated during nasopharygeal stimulation? The objective of this aim is to determine if RVLM neurons (both C1 and non-C1 neurons) are activated during nasopharygeal stimulation in rats. Aim 2: Do RVLM neurons activated during nasopharyngeal stimulation project to the spinal cord? The objective of this aim is to determine whether RVLM neurons (both C1 and non-C1 neurons) that are activated during nasopharygeal stimulation project to the spinal cord. Aim 3: Does elimination of RVLM C1 neurons, by using spinal cord injections of anti-DbH-saporin, prevent the increase in blood pressure observed during nasopharygeal stimulation? The objective of this aim is to determine if C1, or non-C1, neurons are involved in producing the increase in sympathetic tone during nasopharygeal stimulation. This proposal examines both the basic mechanisms and circuitry by which cardiorespiratory afferents, specifically from the upper respiratory tract, integrate within the brainstem to produce autonomic responses. As such, this research has implications for understanding the etiology of neurogenic hypertension.